This proposal is designed to improve our understanding of the mechanical basis of injury that occurs after eccentric contraction as well as the adaptive mechanisms that protect muscle from further injury. Eccentric contraction-biased exercise (i.e., exercise that causes lengthening of an activated muscle) causes muscle injury and also provides a potent strengthening signal to muscle. Based on the potential application of eccentric contractions to athletics and rehabilitation, it is important to understand the mechanisms by which these contractions cause both injury and strengthening. In this way, rationale rehabilitative procedures can be developed based on sound scientific principles. In addition, since eccentric contraction represents a unique mechanical event, understanding the mechanism of eccentric contractions -induced injury can also provide insights into normal muscle structure-function relationships that exist within skeletal muscle. The specific aims of this proposal are to: (1) to determine the relative role that mechanical properties play (primarily stress and strain) in causing muscle injury, (2) to understand mechanisms of stress transmission in muscle fibers by measuring the strain field across the costameric and myofibrillar structures during passive fiber elongation and, (3) to measure the relative strengthening ability of normal muscles compared to muscles devoid of the intermediate filament protein desmin. We hypothesize that the potent effects of eccentric contraction on muscle are due to the injury response initiated and are potentiated by the high muscle stresses that go along with eccentric contractions. These studies not only provide insights into the damage mechanism, but also shed light on important structure-function relationships in normal muscle.